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Growth hormone is increased in the lungs and enhances experimental lung metastasis of melanoma in DJ-1 KO mice

Authors :
Houng-Chi Liou
Ming-Jen Lee
Chia-Hung Chien
Horng-Huei Liou
Wen-Mei Fu
Source :
BMC Cancer
Publication Year :
2016
Publisher :
BioMed Central, 2016.

Abstract

Background Growth hormone (GH) mainly serves an endocrine function to regulate somatic growth, but also serves an autocrine function in lung growth and pulmonary function. Several recent studies have demonstrated the role of autocrine GH in tumor progression in some organs. However, it is not clear whether excessive secretion of GH in the lungs is related to pulmonary nodule formation. Methods Firstly, the lung tissues dissected from mice were used for Western blotting and PCR measurement. Secondly, the cultured cells were used for examining effects of GH on B16F10 murine melanoma cells. Thirdly, male C57BL/6 mice were intravenously injected with B16F10 cells and then subcutaneously injected with recombinant GH twice per week for three weeks. Finally, stably transfected pool of B16F10 cells with knockdown of growth hormone receptor (GHR) was used to be injected into mice. Results We found that expression of GH was elevated in the lungs of DJ-1 knockout (KO) mice. We also examined the effects of GH on the growth of cultured melanoma cells. The results showed that GH increased proliferation, colony formation, and invasive capacity of B16F10 cells. In addition, GH also increased the expression of matrix metalloproteinases (MMPs) in B16F10 cells. Administration of GH in vivo enhanced lung nodule formation in C57/B6 mice. Increased lung nodule formation in DJ-1 KO mice following intravenous injection of melanoma cells was inhibited by GHR knockdown in B16F10 cells. Conclusions These results indicate that up-regulation of GH in the lungs of DJ-1 KO mice may enhance the malignancy of B16F10 cells and nodule formation in pulmonary metastasis of melanoma. Electronic supplementary material The online version of this article (doi:10.1186/s12885-016-2898-5) contains supplementary material, which is available to authorized users.

Details

Language :
English
ISSN :
14712407
Volume :
16
Database :
OpenAIRE
Journal :
BMC Cancer
Accession number :
edsair.doi.dedup.....d3ab4b1cd06afa7da9681681146bc753